Structural Basis for CAL1-Mediated Centromere Maintenance

Medina-Pritchard, B.; Lazou, V.; Zou, J.; Byron, O.; Rappsilber, J.; Heun, P.; Jeyaprakash, A. A.

doi:10.1101/723213

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bioRxiv · 10.1101/723213

Structural Basis for CAL1-Mediated Centromere Maintenance

Medina-Pritchard, B.·Lazou, V.·Zou, J.·Byron, O.·Rappsilber, J.·Heun, P.·Jeyaprakash, A. A.

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Abstract

Centromeres are microtubule attachment sites on chromosomes defined by the enrichment of CENP-A-containing nucleosomes. To preserve centromere identity, CENP-A must be escorted to centromeres by a CENP-A-specific chaperone for deposition. Despite this essential requirement, many eukaryotes differ in the composition of players involved in centromere maintenance highlighting the plasticity of this process. In humans, CENP-A recognition and centromere targeting is achieved by HJURP and the Mis18 complex, respectively. Here, using crystal structures, we show how Drosophila CAL1, an evolutionarily distinct CENP-A chaperone, targets CENP-A to the centromere receptor CENP-C without the requirement of the Mis18 complex: while the N-terminal CAL1 fragment (CAL11-160) wraps around CENP-A/H4 through multiple physical contacts, the C-terminal CAL1 fragment (CAL1893-914) directly binds CENP-C cupin dimer. Our work shows CAL1, though divergent at the primary structure, employs evolutionarily conserved and adaptive structural principles to recognise CENP-A/H4 and CENP-C providing insights into the minimalistic principles underlying centromere maintenance.

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Medina-Pritchard, B., Lazou, V., Zou, J., Byron, O., Rappsilber, J., Heun, P., Jeyaprakash, A. A.. 2019-08-02. Structural Basis for CAL1-Mediated Centromere Maintenance. https://doi.org/10.1101/723213

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